Coexistence of a novel WISP3 pathogenic variant and an MEFV mutation in an Arabic family with progressive pseudorheumatoid dysplasia mimicking polyarticular juvenile idiopathic arthritis.

Autor: Fathalla BM; Section of Pediatric Rheumatology, Department of Medical Subspecialties, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates. bmfathalla@ajch.ae., Elgabaly EA; Department of Radiology, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates., Tayoun AA; Department of Genomics, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
Jazyk: angličtina
Zdroj: Pediatric rheumatology online journal [Pediatr Rheumatol Online J] 2020 Sep 07; Vol. 18 (1), pp. 69. Date of Electronic Publication: 2020 Sep 07.
DOI: 10.1186/s12969-020-00462-5
Abstrakt: Background: A spectrum of rare noninflammatory disorders may present with arthropathy that arises from bony dysplasia, a thickened synovium, and noninflammatory effusion, leading to a constellation of clinical features that mimics chronic polyarticular juvenile idiopathic arthritis (JIA). We report a unique Arabic family harboring a novel pathogenic variant in the WISP3 gene and presenting with progressive pseudorheumatoid dysplasia (PPRD), a rare noninflammatory arthropathy mimicking polyarticular JIA.
Case Presentation: An Arabic family with PPRD was diagnosed using whole-exome sequencing (WES), revealing a novel c.707delG pathogenic variant in the WISP3 gene. The proband was referred at 10 years old for possible diagnosis of polyarticular JIA based on progressive arthropathy for three years. He was already on naproxen and methotrexate. We suspected familial noninflammatory arthropathy based on clinical manifestations, imaging findings, and family history. WES confirmed the molecular diagnosis of PPRD in the proband and one sister with a similar phenotype. An unexpected p.A744S MEFV pathogenic variant was detected in the proband, parents, and affected sister.
Conclusions: Early identification and diagnosis of familial noninflammatory arthropathies such as PPRD can prevent unnecessary use of immunosuppressive medications. Diagnosis requires high suspicion in children with early onset arthritic changes, absence of elevated inflammatory markers, specific imaging findings, and positive family history suggestive of an autosomal recessive disorder. We highlight the advantages of WES over single-gene analysis in such cases.
Databáze: MEDLINE
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